ALDOSTERONE, BODY FAT, AND DIETARY SHIFTS

醛固酮、身体脂肪和饮食变化

基本信息

批准号：
3232670
负责人：
LYNN D DEVENPORT
金额：
$ 8.67万
依托单位：
UNIVERSITY OF OKLAHOMA
依托单位国家：
美国
项目类别：
财政年份：
1984
资助国家：
美国
起止时间：
1984-08-01 至 1990-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3232670
关键词：
adipose tissue albino rat aldosterone corticosterone glucocorticoids hormone receptor hormone regulation /control mechanism lipolysis mineralocorticoids nutrient intake activity nutrition related tag obesity protein metabolism triglycerides

项目摘要

Aldosterone may exert a unique metabolic action. It seems to inhibit the mobilization of energy from body fat and protein stores, and slows liver triglyceride synthesis. Confirmation of this conclusion is one of our objectives, and requires the in vitro lipolysis, protein turnover, and triglyceride studies that we propose. These studies will also provide additional critical information concerning whether aldosterone acts directly on cell machinery or through some other hormone or neurotransmitter. As a probable consequence of this altered metabolism, feeding behavior is changed. Not only is food intake augmented, but if given the opportunity, all excess calories are taken as dietary fat. This accelerates the weight gain, but also raises the possibility of abnormally high serum triglyceride levels and the attendant implications for atherogenesis and carcinogenesis. Accordingly, we propose to evaluate the degree of serum lipid excess engendered by aldosterone when rats are free to choose among the three macronutrients. The pattern of feeding may be changed as well. When feeding ad libitum, aldosterone-infused animals seem to abandon mealeating for nibbling. We propose to give this possibility a careful investigation, allowing free expression of the preferred feeding pattern, then artificially compressing intake, but not limiting calories. Evidence suggests that nibbling is an effective compensative strategy. Important advances in steroid ligand-receptor biochemistry have been made in the past three years. The findings indicate that the mineralocorticoid and glucocorticoid dichotomy is not honored by target tissue. Our work closely fits the new view that these hormones share the same receptor site, with glucocorticoids also acting on another (low affinity) receptor. If true, much confusion as to the metabolic action of steroids could be resolved, not by reference to the hormone type, but to the set of opponent- function receptors involved. We propose to do this through the use of relatively pure receptor agonists, and by a dose-response study of glucocorticoids that is expected to exhibit clear evidence of dual metabolic function, one corresponding to peaks, the other to basal levels of glucocorticoids.

醛固酮可能发挥独特的代谢作用。似乎抑制体内脂肪和蛋白质的能量动员存储，并减慢肝脏甘油三酸酯的合成。确认这个结论是我们的目标之一，需要体外脂解，蛋白质更新和甘油三酸酯研究我们提出。这些研究还将提供其他关键有关醛固酮是否直接在细胞上作用的信息机械或通过其他激素或神经递质。作为这种改变的新陈代谢的可能结果，进食行为已更改。不仅可以增加食物的摄入量，而且如果鉴于机会，所有多余的卡路里被视为饮食脂肪。这加速了体重增加，但也提高了异常高的血清甘油三酸酯水平和服务员对动脉粥样硬化和致癌作用的影响。因此，我们建议评估血清脂质过量的程度当大鼠可以自由选择时，由醛固酮引起三种大量营养素。喂食的模式可能会改变也是如此。随意喂养醛固酮的动物时似乎放弃了用餐。我们建议给这个可能仔细调查，允许自由表达首选的喂食模式，然后人为地压缩摄入量，但不要限制卡路里。有证据表明，ni是一个有效的补偿策略。类固醇配体生物化学的重要进展具有是在过去三年中制作的。调查结果表明矿物皮质激素和糖皮质激素二分法没有受到尊重靶组织。我们的工作非常适合这些新观点激素共享相同的受体部位，糖皮质激素也作用于另一个（低亲和力）受体。如果是真的，很多混乱关于类固醇的代谢作用，可以解决引用激素类型，但对对手的集合 - 涉及功能受体。我们建议通过使用相对纯的受体激动剂，并通过剂量反应糖皮质激素的研究有望表现出明确的证据双重代谢功能，一个与峰相对应，另一个对应于峰到基础糖皮质激素的基础水平。